The proposed project is to study factors controlling the proliferation and maturation of granulocytes in vivo and in vitro. The major emphasis is directed toward the study of in vitro proliferation of colonies of granulocytes and mononuclear cells from blood and marrow of animals and man. Colonies are grown in a soft gel system (agar- methycellulose) in the presence of a colony stimulating factor (CSF). Human and animal cells will also be cultured in vivo by using the millipore diffusion chamber technique. Studies will include the following: 1) to determine if stimulated lymphocytes produce a CSF specific for certain lines, 2) to study the relationship of CSF from lymphocytes and other lymphokines such as migration inhibition factor (MIF) and lymphotoxin, 3) to determine if CSF is produced within the cytoplasm of the cell or in the cell membrane, 4) to determine the mechanism of action of CSF in inducing cell proliferation and maturation, 5) to attempt to quantitate the number of stem cells in various diseases such as aplastic anemia and granulocytopenia, 6) to determine the pattern of colony formation in patients with polycythemia vera, myelofibrosis and leukemia, 7) to determine the relationship between the pattern of cell proliferation in leukemia and response to therapy, and 8) to determine the proliferation and maturation of hematopoietic cells in vivo using the millipore diffusion chamber technique.